The neocortex comprises 80% of brain volume in humans, and it is essential for normal sensation, movement and cognition. Enormous effort has been expended attempting to understand the many functions of the neocortex. Basic studies of the physiology of its neurons, synapses and local circuits have benefitted immeasurably from the development of in vitro slice preparations over the past 2 decades. However, a question that has plagued in vitro physiologists from the beginning is: how do neurons in isolated preparations differ from neurons in the intact brain? A related question is: to what extent do traditional methods of intracellular recording with sharp microelectrodes perturb and distort the neuronal properties being measured? The answers are critically important. No one would argue that a neuron in vitro behaves entirely like a neuron in vivo but precisely how they differ can so far only be guessed. The goal of this project is to study the cellular properties of neocortical neurons in their natural milieu, in vivo, using methods of whole-cell patch recording to minimize cellular trauma. This approach will clarify differences between neurons in isolated and intact brains, and allow experiments that were not feasible with traditional recording methods. Neurons will be recorded with whole-cell methods from the primary somatosensory cortex of anesthetized rats, and from the same area in isolated slices. Recordings will be made from both cell bodies and apical dendrites. Natural sensory stimuli, consisting of controlled deflections of the facial vibrissae, will be used for many of the in vivo experiments. Several hypotheses that have arisen from studies in vitro will be tested in the intact animal. There are three specific questions: l) How do the passive and active membrane properties of different classes of neurons (soma.ta and dendrites) in vivo differ from those characterized in vitro? 2) Do the intrinsic physiological properties of a neuron predict the type of synaptic input it receives during natural sensory stimulation? 3) What are the mechanisms of GABAergic inhibition onto somata and dendrites in the intact neocortex? The results should reveal important differences and similarities between neocortical neurons in vitro and in vivo. Information about the biophysical properties of neurons in their natural environment will be essential to understand how the neocortex effects normal and pathological behaviors.